Table 2. Inter-tissue age-dysregulated functions.

Brain-Liver
Related function	Summary network description	No. of nodes	Genes involved - Brain	Genes involved - Liver	WGCNA expression trend - Brain	WGCNA expression trend - Liver	WGCNA expression shift - Brain	WGCNA expression shift - Liver
Immune response	Response immune mediated immunoglobulin	13	B2m, C1qa, C1qb, C1qc, C3, C4b, Ctsh, Gbp3, H2-D1, H2-K1, H2-T23, Il33, Irf7, Itgb2, Lag3, Lgals3, Lyz2, Slc11a1, Tap2	Cd19, Cd79a, Cd79b, H2-Aa, H2-Eb1, Ighm, Igkc, Iglc2, Jchain, Slamf7	Increase	Increase	Middle to old-age - 15-18 months	Adulthood to Middle-age - 6-9 months and 9-12 months
	regulation production cell proliferation	26	B2m, C1qa, C1qc, C3, Csf1, Ctsz, Cx3cr1, H2-D1, H2-K1, H2-T23, Il33, Itgb2, Lag3, Lgals3, Slc11a1, Tap2	Ccl5, Cd19, Cd79a, H2-Aa, Ighm, Igkv3-5, Mzb1, Ntrk2, Slamf7	Increase	Increase	Middle to old-age - 15-18 months	Middle-age - 9-12 months
	processing presentation peptide antigen	4	B2m, Ctss, H2-D1, H2-K1, H2-T23, Psmb8, Slc11a1, Tap2, Tapbp	H2-Eb1, H2-Aa	Increase	Increase	Middle to old-age - 15-18 months	Middle-age - 9-12 months
Brain-Muscle
Related function	Summary network description	No. of nodes	Genes involved - Brain	Genes involved - Muscle	WGCNA expression trend - Brain	WGCNA expression trend - Muscle	WGCNA expression shift - Brain	WGCNA expression shift - Muscle
Tissue regeneration	angiogenesis	1	C3, Lgals3, Itgb2, Ctsh, Cx3cr1	Fn1, Serpinf1, Sparc, Cd34, Anxa2	Increase	Decrease	Middle to old-age - 15-18 months	Middle-age - 9-12 months
	glial cell migration	1	Csf1, Hexb	Fn1, Ndn, Lrp1	Increase	Decrease	Middle to old-age - 15-18 months	Middle-age - 9-12 months
	extracellular structure organization response	3	C3, Ctss, Gfap, Lgals3, Neat1, Slc11a1	Anxa2, Cd34, Col3a1, Col5a1, Col5a2, Fn1, Lrp1, Nid1, Serping1, Tgfbi	Increase	Decrease	Middle to old-age - 15-18 months	Middle-age - 9-12 months
	regulation peptidase activity	1	Serpina3n, Ctsh, Psmb8, Ctsd	Serpinf1, Pi16, Serping1, Timp2	Increase	Decrease	Middle to old-age - 15-18 months	Middle-age - 9-12 months
Heart-Muscle
Related function	Summary network description	No. of nodes	Genes involved - Heart	Genes involved - Muscle	WGCNA expression trend – Heart	WGCNA expression trend - Muscle	WGCNA expression shift - Heart	WGCNA expression shift - Muscle
Energy metabolism	respiratory electron transport atp	6	Coq9, Cyc1, Eno3, Ndufa10, Ndufs2, Sdhd, Slc25a12, Uqcrc1	Atp5l, Atp5g3, Cox5a, Ndufa8	Decrease	Increase (males)	Old-age - 18-21 months	Middle-age - 9-12 months
Liver-Heart
Related function	Summary network description	No. of nodes	Genes involved - Liver	Genes involved - Heart	WGCNA expression trend – Liver	WGCNA expression trend - Heart	WGCNA expression shift - Liver	WGCNA expression shift - Heart
Glucocorticoid signaling	receptor signaling pathway glucocorticoid	3	Ntrk2	Ppp5c, Phb	Increase	Decrease	Middle-age - 9-12 months	Old-age - 18-21 months
Liver-Muscle
Related function	Summary network description	No. of nodes	Genes involved - Liver	Genes involved - Muscle	WGCNA expression trend – Liver	WGCNA expression trend - Muscle	WGCNA expression shift - Liver	WGCNA expression shift - Muscle
Response to amino acid stimulus	cellular response to amino acid stimulus	1	Ntrk2	Col3a1, Col5a2, Col6a1	Increase	Decrease	Middle-age - 9-12 months	Middle-age - 9-12 months

In the sex-associated modules, the sex in which the genes are enriched is indicated inside parentheses. Relates to Supplementary Table 8.